The focus of this line of investigation is to compare short-term vs long-term neuroendocrine challenges on the proliferation of splenic lymphocytes. This was accomplished by comparing the in vitro proliferative response of lymphocytes to concanavalin A following an in vivo 4 hour isoproterenol treatment compared to a 5 day constant infusion of isoproterenol. Following the short- term isoproterenol treatment splenic lymphocyte proliferation was inhibited compared to controls, while long-term exposure resulted in an increase in proliferative response. These results were not related to corticosterone levels which were elevated in both the acute and chronic treatments, nor were they related to the presence of the adrenal gland. These studies suggest that splenic lymphocytes become insensitive to the suppressive effect of chronically elevated glucocorticoid.